Subclassification of newly diagnosed glioblastomas through an immunohistochemical approach.
Subclassification of newly diagnosed glioblastomas through an immunohistochemical approach.
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DOI：
10.1371/journal.pone.0115687
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
den Dunnen WF
中科院分区：
文献类型：
--
作者：
Conroy S;Kruyt FA;Joseph JV;Balasubramaniyan V;Bhat KP;Wagemakers M;Enting RH;Walenkamp AM;den Dunnen WF
已经描述了胶质母细胞瘤（GBM）中与临床结果和对治疗的反应相关的分子特征。原神经（PN）和间充质（MES）的签名已被确定为最一致，但其他包括经典（CLAS）也有报道。已经通过阵列技术在RNA和DNA水平上检测分子特征，但是这些方法成本高，并且不能考虑肿瘤内不同细胞的个体贡献。因此，本研究的目的是调查是否可以通过应用标准病理学实验室程序评估和分配新诊断的GBM亚类。分析了123例新诊断的GBM的23种预先鉴定的蛋白质的肿瘤细胞表达和EGFR扩增，一起允许对65%的肿瘤进行亚分类。发现基于免疫组织化学（IHC）的分析类似于使用PN和MES亚类的9-基因转录特征的基于转录的分析。基于这些数据，提出了一种新的，最小的基于IHC的GBM子类分配方案。IDH 1 R132 H的阳性染色可用于PN亚类分配、CLAS亚类的高EGFR表达和MES亚类的PTEN、Vim和/或YKL 40的组合高表达。在一个独立的肿瘤集，这导致类似的子类分配率在训练集中观察到的应用程序进行了评估。因此，本研究中提出的基于IHC的亚分类方案在未来的个体患者样本分层研究中非常有用。
Molecular signatures in Glioblastoma (GBM) have been described that correlate with clinical outcome and response to therapy. The Proneural (PN) and Mesenchymal (MES) signatures have been identified most consistently, but others including Classical (CLAS) have also been reported. The molecular signatures have been detected by array techniques at RNA and DNA level, but these methods are costly and cannot take into account individual contributions of different cells within a tumor. Therefore, the aim of this study was to investigate whether subclasses of newly diagnosed GBMs could be assessed and assigned by application of standard pathology laboratory procedures. 123 newly diagnosed GBMs were analyzed for the tumor cell expression of 23 pre-identified proteins and EGFR amplification, together allowing for the subclassification of 65% of the tumors. Immunohistochemistry (IHC)-based profiling was found to be analogous to transcription-based profiling using a 9-gene transcriptional signature for PN and MES subclasses. Based on these data a novel, minimal IHC-based scheme for subclass assignment for GBMs is proposed. Positive staining for IDH1R132H can be used for PN subclass assignment, high EGFR expression for the CLAS subtype and a combined high expression of PTEN, VIM and/or YKL40 for the MES subclass. The application of the proposed scheme was evaluated in an independent tumor set, which resulted in similar subclass assignment rates as those observed in the training set. The IHC-based subclassification scheme proposed in this study therefore could provide very useful in future studies for stratification of individual patient samples.
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影响因子：
3.7
作者：
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作者：
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通讯作者：
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